It is known that certain dihydropyridine derivatives have a Ca.sup.2+ -antagonistic action, and are highly useful for treatment of various cardiovascular disorders such as angina pectoris, myocardial infarction, hypertension and cardiac arrythmia. It is further known that beta-adrenoceptor blocking agents are also useful for the treatment of such cardiovascular disorders.
However, the mechanism of actions of dihydropyridine derivatives is entirely different from that of beta-adrenoceptor blocking agents. That is, beta-adrenoceptor blocking agents reduce heart rate, cardiac output, stroke volume, cardiac work and myocardial oxygen demand whereas, Ca.sup.2+ -antagonists improve left ventricular function due to their coronary vasodilating and systemic vasodilating effect (reduction in afterload) and also inhibit coronary vasospasm.
Recently it has been reported that a combined administration of a Ca.sup.2+ -antagonist and a beta-blocker can achieve maximal symptomatic improvement in clinical angina pectoris. [Bassan, M., Weiler-Ravell, D. and Shalev, O.; Additive antianginal effect of verapamil in patients receiving propranolol: Br. Med. J., 284, 1067(1982)]. Further it has been reported that a combined administration of such two kinds of drug can be recommended for the treatment of hypertension, since the side effects of either drug are almost abolished or inhibited by the combination administration of both drugs. That is, beta-blocker inhibits a Ca.sup.2+ -antagonist-induced reflex increase of heart rate; and beta-blocker completely inhibit a Ca.sup.2+ -antagonist-induced increase of plasma renin activity. [Aoki, A., Kondo, S., Mochizuki, A., et al; Antihypertensive effect of Cardiovascular Ca.sup.2+ -antagonist in hypertensive patients in the absence and presence of beta-adrenergic blockade; Am. Heart J., 96, 218 (1978)]
Thus, it would be expected that a compound having both Ca.sup.2+ -antagonistic and beta-blocking activities are of interest in the management of ischemic heart-diseases and hypertension.
However, any compound having such both actions is not known until now. That is, it has never been reported that a compound having both Ca.sup.2+ -antagonistic and beta-blocking activities has been synthesized. Thus the purpose of this invention is to provide novel compounds which have both the actions (namely, Ca.sup.2+ -antagonistic activity and adrenergic beta-receptor blocking activity) and the production methods for the compounds.